Biomedical Engineering Reference
In-Depth Information
Chapter 5
Astrocytic Calcium Signaling: Mechanism and Implications
for Functional Brain Imaging
Xiaohai Wang, Takahiro Takano, and Maiken Nedergaard
Abstract
Astrocytes are electrically non-excitable cells that, on a slow time scale of seconds, integrate synaptic trans-
mission by dynamic increases in cytosolic Ca
2
+
. A number of groups have recently shown that astrocytic
Ca
2
+
signaling regulates vascular tones and that astrocytes play a central role in functional hyperemia
by Ca
2
+
-dependent release of Prostaglandin E2 (PGE
2
). Astrocytes are, however, not simple detectors
of excitatory transmission, since a number of neuromodulator and hormones trigger elevations in astro-
cytic Ca
2
+
independently of synaptic transmission. Furthermore, astrocytes exhibit ex vivo intrinsic Ca
2
+
excitability, or spontaneous increases in Ca
2
+
that are not triggered by receptor activation. The notion
that astrocytes can regulate vascular tone independently of synaptic transmission challenges the notion
that changes in the blood oxygenation level dependent (BOLD) signal is directly proportional to neu-
ronal activity and may thus require a reevaluation of the large body of data accumulated using functional
magnetic resonance imaging (fMRI).
Key words:
Photolysis, 2-photon imaging, functional brain imaging.
1. Introduction
Until about two decades ago, astrocytes were regarded as
non-excitable supporting cells in the brain, lacking membrane
properties required to generate action potentials. The view of
astrocytes as simple supporting cells was questioned in the early
1990s, with the demonstration that glutamate can trigger Ca
2
+
oscillations among cultured glial cells often resulting in propa-
gating intercellular Ca
2
+
waves
(1)
. The notion that astrocytes
can actively propagate Ca
2
+
waves among each other led to the
studies of Ca
2
+
signaling between astrocytes and neurons in
mixed cultures. These studies revealed that astrocytic Ca
2
+
waves
